Comprehensive Cardiovascular and Renal Protection in Patients with Type 2 Diabetes.

Type 2 diabetes (T2DM) is one of the main public health care problems worldwide. It is associated with a marked increased risk of developing atherosclerotic vascular disease, heart failure, chronic kidney disease and death. It is essential to act during the early phases of the disease, through the intensification of lifestyle changes and the prescription of those drugs that have been shown to reduce these complications, with the aim not only of achieving an adequate metabolic control, but also a comprehensive vascular risk control. In this consensus document, developed by the different specialists that treat these patients (endocrinologists, primary care physicians, internists, nephrologists and cardiologists), a more appropriate approach in the management of patients with T2DM or its complications is provided. A particular focus is given to the global control of cardiovascular risk factors, the inclusion of weight within the therapeutic objectives, the education of patients, the deprescription of those drugs without cardiovascular benefit, and the inclusion of GLP-1 receptor agonists and SGLT2 inhibitors as cardiovascular protective drugs, at the same level as statins, acetylsalicylic acid, or renin angiotensin system inhibitors.

PostCOVID effect on endothelial function in hypertensive patients: A new research opportunity.

SARS-CoV-2 is causing devastation both in human lives and economic resources. When the world seems to start overcoming the pandemics scourge, the threat of long-term complications of COVID-19 is rising. Reports show that some of these long-term effects may contribute to the main cause of morbimortality worldwide: the vascular diseases. Given the evidence of damage in the endothelial cells due to SARS-CoV-2 and that endothelial dysfunction precedes the development of arteriosclerosis, the authors propose to measure endothelial function around 6-12 months after acute disease in hypertensive patients, especially if they have other cardiovascular risk factors or overt vascular disease. The methods the authors propose are cost-effective and can be made available to any hypertension unit. These methods could be the "in vivo" assessment of endothelial function by flow mediated vasodilatation after ischemia by Laser-Doppler flowmetry and the measurement of plasma free circulating DNA and microparticles of endothelial origin.

Basal insulin analogues in people with diabetes and chronic kidney disease.

BACKGROUND: Diabetic kidney disease is the leading cause of chronic kidney disease (CKD) and end-stage kidney disease (ESKD) worldwide. ESKD has a high prevalence in patients with diabetes mellitus (DM). CKD increases the chances of hypoglycaemia by different mechanisms, causes insulin resistance and a decrease in insulin metabolism. Both the "Kidney Disease: Improving Global Outcomes" (KDIGO) and "American Diabetes Association" (ADA) guidelines recommend the use of insulin as part of treatment, but the type of basal insulin is not specified. METHODS: We reviewed the literature to determine whether first- and second-generation basal insulins are effective and safe in CKD patients. We reviewed specific pivotal studies conducted by pharmaceutical laboratories, as well as independent studies. CONCLUSIONS: Basal insulins are safe and effective in patients with CKD and diabetes mellitus but we do not have specific studies. Given that CKD is one of the main complications of type 2 DM, and insulin specific treatment in the final stages, the absence of studies is striking. Real-life data are also important since trials such as pivotal studies do not fully represent actual patients. Treatment should be individualized until we have specific trials in this type of population.

Author Correction: A new common functional coding variant at the DDC gene change renal enzyme activity and modify renal dopamine function.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Evaluación del riesgo hemorrágico de la terapia antitrombótica en pacientes con ictus / Bleeding risk assessment for stroke patients on antithrombotic therapy

Introducción: Tras un evento cerebrovascular isquémico el riesgo de recurrencias es elevado, por lo que se hace necesario el uso de terapia antitrombótica para disminuir nuevos eventos. Desarrollo: A pesar de su beneficio, estas terapias aumentan el riesgo de sangrado. Por tanto, determinar qué pacientes presentan mayor riesgo de hemorragia es fundamental. Existen diferentes modelos predictores de hemorragia y, en particular, de hemorragia intracraneal, asociados al uso de antiagregantes en pacientes con ictus isquémico o AIT, como las escalas CCSC, Intracranial-B2LEED3S score o la S2TOP-BLEED. No obstante, mientras que las principales guías internacionales recomiendan el uso de escalas, como HAS-BLED, para evaluar el riesgo de sangrado en pacientes anticoagulados, no existe una recomendación específica en el caso del uso de antiagregantes. Conclusiones: En esta revisión se presentan los principales modelos disponibles en la actualidad para la predicción de sangrado de la terapia antitrombótica en pacientes con ictus o AIT

Introduction: After an ischemic cerebrovascular event the risk of new ischemic events is high, therefore antithrombotic therapy are indicated to prevent stroke recurrence. Discussion: Despite its clear benefit, these therapies increase the risk of bleeding. Therefore, it is essential to identify high hemorrhagic risk patients. There are different predictive models of hemorrhage, in particular of intracranial hemorrhage, associated with the use of antiaggregants in patients who have presented an ischemic stroke or TIA, such as the CCSC, intracranial scales -B2LEED3S score or S2TOP-BLEED. However, though main international guidelines recommend the use of scales, in particular, the HAS-BLED score, to assess the risk of bleeding in anticoagulated patients, there is no specific recommendation in the case of the use of antiplatelet drugs. Conclusions: In this review we present the main models currently available for the prediction of bleeding of antithrombotic therapy in patients who have had a stroke or TIA

Cetoacidosis diabética grave, fracaso renal agudo y deshidratación por canagliflozina en paciente con diabetes mellitus tipo 2: presentación clínica atípica / Severe diabetic ketoacidosis, acute kidney injury and dehydration due to canagliflozin in type 2 diabetes mellitus patient: Atypical clinical presentation

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Real-life experience with Dulaglutide: Analysis of clinical effectiveness to 24 months.

OBJECTIVE: Dulaglutide is an agonist of "glucagon-like peptide type 1″ receptors (arGLP1). The clinical efficacy of this molecule is based on reductions in glycosylated hemoglobin (HbA1c) and weight, data shown in the pivotal AWARD studies. METHODS: We propose a retrospective and multicenter study that allows evaluating the effectiveness of dulaglutide at 24 months after treatment began, under conditions of usual clinical practice, and comparing the results obtained with those that are reflected in the controlled trials. RESULTS: The results show a reduction in the HbA1c levels -1.4% at 6 M and this reduction were maintained throughout 12 M and 24 M (p < 0.001). Plasma glucose showed significant reductions around -30 mg / dL at 6 months (p < 0.001) that remained until the end of the follow-up at 12 and 24 M, respectively. The weight decreased significantly at 6 M (p < 0.001) but continued decreasing at 12 and 24 M, showing statistically significant differences (p: 0.001). CONCLUSIONS: Our results are similar to those obtained in pivotal clinical trials and confirm these benefits in real life.

Statins in Ischemic Stroke Prevention: What Have We Learned in the Post-SPARCL (The Stroke Prevention by Aggressive Reduction in Cholesterol Levels) Decade?

PURPOSE OF REVIEW: We describe the current status of lipid-lowering therapies for ischemic stroke prevention. The SPARCL trial published in 2006 has been a landmark study in vascular neurology. The trial demonstrated that high-dose atorvastatin prevents recurrent stroke, and led the AHA/ASA to recommend statin therapy for patients with stroke or TIA of atherosclerotic origin. RECENT FINDINGS: Recently, the J-STARS study demonstrated that therapy with low-dose pravastatin reduced atherothrombotic infarction incidence among patients with prior ischemic stroke. Besides, several trials have shown improved stroke outcomes with non-statin lipid-lowering medications: IMPROVE-IT with ezetimibe on top of simvastatin and PCSK9 inhibitors-FOURIER with evocolumab and ODYSSEY-OUTCOMES with alirocumab-on top of statin therapy. LDL-cholesterol remains the primary lipid treatment target for reduction of stroke risk. Randomized trials have shown that each reduction of 40 mg/dL in the level of LDL-cholesterol reduces the stroke risk by approximately one quarter, and further, reductions in LDL-cholesterol levels have shown to produce additional reductions in stroke risk. Currently, we have evidence of benefit for adding non-statin lipid-modifying therapies to statins to reduce stroke risk. Surely, these novel strategies to reduce residual lipidic risk will provide future benefits on stroke prevention.

Bleeding risk assessment for stroke patients on antithrombotic therapy. / Evaluación del riesgo hemorrágico de la terapia antitrombótica en pacientes con ictus.

INTRODUCTION: After an ischemic cerebrovascular event the risk of new ischemic events is high, therefore antithrombotic therapy are indicated to prevent stroke recurrence. DISCUSSION: Despite its clear benefit, these therapies increase the risk of bleeding. Therefore, it is essential to identify high hemorrhagic risk patients. There are different predictive models of hemorrhage, in particular of intracranial hemorrhage, associated with the use of antiaggregants in patients who have presented an ischemic stroke or TIA, such as the CCSC, intracranial scales -B2LEED3S score or S2TOP-BLEED. However, though main international guidelines recommend the use of scales, in particular, the HAS-BLED score, to assess the risk of bleeding in anticoagulated patients, there is no specific recommendation in the case of the use of antiplatelet drugs. CONCLUSIONS: In this review we present the main models currently available for the prediction of bleeding of antithrombotic therapy in patients who have had a stroke or TIA.

A new common functional coding variant at the DDC gene change renal enzyme activity and modify renal dopamine function.

The intra-renal dopamine (DA) system is highly expressed in the proximal tubule and contributes to Na+ and blood pressure homeostasis, as well as to the development of nephropathy. In the kidney, the enzyme DOPA Decarboxylase (DDC) originating from the circulation. We used a twin/family study design, followed by polymorphism association analysis at DDC locus to elucidate heritable influences on renal DA production. Dense single nucleotide polymorphism (SNP) genotyping across the DDC locus on chromosome 7p12 was analyzed by re-sequencing guided by trait-associated genetic markers to discover the responsible genetic variation. We also characterized kinetics of the expressed DDC mutant enzyme. Systematic polymorphism screening across the 15-Exon DDC locus revealed a single coding variant in Exon-14 that was associated with DA excretion and multiple other renal traits indicating pleiotropy. When expressed and characterized in eukaryotic cells, the 462Gln variant displayed lower Vmax (maximal rate of product formation by an enzyme) (21.3 versus 44.9 nmol/min/mg) and lower Km (substrate concentration at which half-maximal product formation is achieved by an enzyme.)(36.2 versus 46.8 µM) than the wild-type (Arg462) allele. The highly heritable DA excretion trait is substantially influenced by a previously uncharacterized common coding variant (Arg462Gln) at the DDC gene that affects multiple renal tubular and glomerular traits, and predicts accelerated functional decline in chronic kidney disease.

La entrevista clínica y el teléfono móvil / Clinical interview and mobile phone

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Hematoma cerebral masivo con alteraciones electrocardiográficas / Massive cerebral hematoma with electrocardiographic abnormalities

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